Abstract：
:Cyclic dinucleotides (CDNs) play central roles in bacterial pathogenesis and innate immunity. The mammalian enzyme cGAS synthesizes a unique cyclic dinucleotide (cGAMP) containing a 2'-5' phosphodiester linkage essential for optimal immune stimulation, but the molecular basis for linkage specificity is unknown. Here, we show that the Vibrio cholerae pathogenicity factor DncV is a prokaryotic cGAS-like enzyme whose activity provides a mechanistic rationale for the unique ability of cGAS to produce 2'-5' cGAMP. Three high-resolution crystal structures show that DncV and human cGAS generate CDNs in sequential reactions that proceed in opposing directions. We explain 2' and 3' linkage specificity and test this model by reprogramming the human cGAS active site to produce 3'-5' cGAMP, leading to selective stimulation of alternative STING adaptor alleles in cells. These results demonstrate mechanistic homology between bacterial signaling and mammalian innate immunity and explain how active site configuration controls linkage chemistry for pathway-specific signaling.
journal_name
Celljournal_title
Cellauthors
Kranzusch PJ,Lee ASY,Wilson SC,Solovykh MS,Vance RE,Berger JM,Doudna JAdoi
10.1016/j.cell.2014.07.028subject
Has Abstractpub_date
2014-08-28 00:00:00pages
1011-1021issue
5eissn
0092-8674issn
1097-4172pii
S0092-8674(14)00978-7journal_volume
158pub_type
杂志文章相关文献
CELL文献大全abstract：:When treated with the synthetic glucocorticoid dexamethasone, HT1080 human fibrosarcoma cells show changes in morphology, adhesion, and the extracellular matrix. Dexamethasone treatment results in a tenfold increase in the rate of fibronectin biosynthesis in HT1080 cells and a twofold increase in untransformed, normal...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(83)90357-4
更新日期：1983-05-01 00:00:00
abstract：:Natural killer (NK) cells play a key role in innate immunity by detecting alterations in self and non-self ligands via paired NK cell receptors (NKRs). Despite identification of numerous NKR-ligand interactions, physiological ligands for the prototypical NK1.1 orphan receptor remain elusive. Here, we identify a viral ...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2017.03.002
更新日期：2017-03-23 00:00:00
abstract：:The segment polarity genes engrailed and wingless are expressed in neighboring stripes of cells on opposite sides of the Drosophila parasegment boundary. Each gene is mutually required for maintenance of the other's expression; continued expression of both also requires several other segment polarity genes. We show he...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(92)90264-d
更新日期：1992-10-02 00:00:00
abstract：:Viruses are adept at evolving or co-opting genomic elements that allow them to maximize their replication potential in the infected host. This evolutionary plasticity makes viruses an invaluable system to identify new mechanisms used not only by viruses but also by vertebrate cells to modulate gene expression. Here, I...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2009.01.048
更新日期：2009-02-20 00:00:00
abstract：:An "off-the-shelf" cell therapy derived from induced pluripotent stem cells (iPSCs) has entered clinical trials in the United States. Other companies are following suit, harnessing iPSCs' self-renewal ability to manufacture cell therapies that don't require customization for each patient. But some experts aren't sure ...
journal_title：Cell
pub_type： 杂志文章,评审
doi：10.1016/j.cell.2019.05.043
更新日期：2019-06-13 00:00:00
abstract：:The mesenchymal-amoeboid transition (MAT) was proposed as a mechanism for cancer cells to adapt their migration mode to their environment. While the molecular pathways involved in this transition are well documented, the role of the microenvironment in the MAT is still poorly understood. Here, we investigated how conf...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2015.01.007
更新日期：2015-02-12 00:00:00
abstract：:The Polycomb group (Pc-G) proteins are responsible for keeping developmental regulators, like homeotic genes, stably and inheritably repressed during Drosophila development. Several similarities to a protein class involved in heterochromatin formation suggest that the Pc-G exerts its function at the higher order chrom...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(93)90328-n
更新日期：1993-12-17 00:00:00
abstract：:Genetic alterations in signaling pathways that control cell-cycle progression, apoptosis, and cell growth are common hallmarks of cancer, but the extent, mechanisms, and co-occurrence of alterations in these pathways differ between individual tumors and tumor types. Using mutations, copy-number changes, mRNA expressio...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2018.03.035
更新日期：2018-04-05 00:00:00
abstract：:The mammalian BAF complex regulates gene expression by modifying chromatin structure. In this report, we identify 80 genes activated and 2 genes repressed by the BAF complex in SW-13 cells. We find that prior binding of NFI/CTF to the NFI/CTF binding site in CSF1 promoter is required for the recruitment of the BAF com...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/s0092-8674(01)00446-9
更新日期：2001-08-10 00:00:00
abstract：:We have shown that covalent conjugation of ubiquitin to proteins is temperature-sensitive in the mouse cell cycle mutant ts85 due to a specifically thermolabile ubiquitin-activating enzyme (accompanying paper). We show here that degradation of short-lived proteins is also temperature sensitive in ts85 , in contrast to...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(84)90300-3
更新日期：1984-05-01 00:00:00
abstract：:Nuclear DNA from eucaryotes contains a significant fraction which forms duplexes very rapidly and also independently of the DNA concentration. This fraction can be isolated by adsorption to hydroxylapatite and has been called foldback DNA (Britten and Smith, 1970). Here we extend previous studies to show that the fold...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(76)90182-3
更新日期：1976-05-01 00:00:00
abstract：:Mucus production by goblet cells of the large intestine serves as a crucial antimicrobial protective mechanism at the interface between the eukaryotic and prokaryotic cells of the mammalian intestinal ecosystem. However, the regulatory pathways involved in goblet cell-induced mucus secretion remain largely unknown. He...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2014.01.026
更新日期：2014-02-27 00:00:00
abstract：:Potassium is an essential mineral element for plant growth and development. Although it is known that plants absorb and transport K+ through membrane transporters, it remains unclear how these transporters are regulated. Here we show that the protein kinase CIPK23, encoded by the LKS1 gene, regulates K+ uptake under l...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2006.06.011
更新日期：2006-06-30 00:00:00
abstract：:Macroautophagy is a lysosomal degradative pathway essential for neuron survival. Here, we show that macroautophagy requires the Alzheimer's disease (AD)-related protein presenilin-1 (PS1). In PS1 null blastocysts, neurons from mice hypomorphic for PS1 or conditionally depleted of PS1, substrate proteolysis and autopha...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2010.05.008
更新日期：2010-06-25 00:00:00
abstract：:Loss-of-function diseases are often caused by a mutation in a protein traversing the secretory pathway that compromises the normal balance between protein folding, trafficking, and degradation. We demonstrate that the innate cellular protein homeostasis, or proteostasis, capacity can be enhanced to fold mutated enzyme...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2008.06.037
更新日期：2008-09-05 00:00:00
abstract：:Prolonged behavioral challenges can cause animals to switch from active to passive coping strategies to manage effort-expenditure during stress; such normally adaptive behavioral state transitions can become maladaptive in psychiatric disorders such as depression. The underlying neuronal dynamics and brainwide interac...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2019.02.037
更新日期：2019-05-02 00:00:00
abstract：:The loss of expression of particular microRNAs can contribute to tumorigenesis. Kota et al. (2009) now explore in a mouse model a promising new approach for the treatment of liver cancer-re-establishing the expression of an miRNA using a viral vector. ...
journal_title：Cell
pub_type： 评论,杂志文章
doi：10.1016/j.cell.2009.05.038
更新日期：2009-06-12 00:00:00
abstract：:The organization of a cell emerges from the interactions in protein networks. The interactome is critically dependent on the strengths of interactions and the cellular abundances of the connected proteins, both of which span orders of magnitude. However, these aspects have not yet been analyzed globally. Here, we have...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2015.09.053
更新日期：2015-10-22 00:00:00
abstract：:Hematopoietic stem cells (HSCs) develop from a specialized subpopulation of endothelial cells known as hemogenic endothelium (HE). Although the HE origin of HSCs is now well established in different species, the signaling pathways that control this transition remain poorly understood. Here, we show that activation of ...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2013.08.055
更新日期：2013-09-26 00:00:00
abstract：:We have isolated two adenylyl cyclase genes, designated ACA and ACG, from Dictyostelium. The proposed structure for ACA resembles that proposed for mammalian adenylyl cyclases: two large hydrophilic domains and two sets of six transmembrane spans. ACG has a novel structure, reminiscent of the membrane-bound guanylyl c...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(92)90411-5
更新日期：1992-04-17 00:00:00
abstract：:Signaling by the epidermal growth factor receptor requires an allosteric interaction between the kinase domains of two receptors, whereby one activates the other. We show that the intracellular juxtamembrane segment of the receptor, known to potentiate kinase activity, is able to dimerize the kinase domains. The C-ter...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2009.04.025
更新日期：2009-06-26 00:00:00
abstract：:Expression of pipe in the somatic tissue of the Drosophila ovary is required for the formation of embryonic dorsal-ventral polarity. pipe, which encodes an enzyme similar to the glycosaminoglycan-modifying enzyme heparan sulfate 2-O-sulfotransferase, is expressed in a spatially restricted domain of follicle cells on t...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/s0092-8674(00)81615-3
更新日期：1998-11-13 00:00:00
abstract：:The therapeutic value of DNA-damaging antineoplastic agents is dependent upon their ability to induce tumor cell apoptosis while sparing most normal tissues. Here, we show that a component of the apoptotic response to these agents in several different types of tumor cells is the deamidation of two asparagines in the u...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/s0092-8674(02)00972-8
更新日期：2002-10-04 00:00:00
abstract：:It has been long appreciated that, during meiosis, DNA replication is coordinated with the subsequent formation of the double-strand breaks (DSBs) that initiate recombination, but a mechanistic understanding of this process was elusive. We now show that, in yeast, the replisome-associated components Tof1 and Csm3 phys...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2014.06.028
更新日期：2014-08-14 00:00:00
abstract：:The increasing proportion of variance in human complex traits explained by polygenic scores, along with progress in preimplantation genetic diagnosis, suggests the possibility of screening embryos for traits such as height or cognitive ability. However, the expected outcomes of embryo screening are unclear, which unde...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2019.10.033
更新日期：2019-11-27 00:00:00
abstract：:Tumor suppressors block the development of cancer and are often lost during tumor development. Papa et al. show that partial loss of normal PTEN tumor suppressor function can be compounded by additional disruption caused by the expression of inactive mutant PTEN protein. This has significant implications for patients ...
journal_title：Cell
pub_type： 评论,杂志文章
doi：10.1016/j.cell.2014.04.008
更新日期：2014-04-24 00:00:00
abstract：:Transcriptional regulation by the glucocorticoid receptor (GR) is mediated by hormone binding, receptor dimerization, and coactivator recruitment. Here, we report the crystal structure of the human GR ligand binding domain (LBD) bound to dexamethasone and a coactivator motif derived from the transcriptional intermedia...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/s0092-8674(02)00817-6
更新日期：2002-07-12 00:00:00
abstract：:Membrane traffic in eukaryotic cells involves transport of vesicles that bud from a donor compartment and fuse with an acceptor compartment. Common principles of budding and fusion have emerged, and many of the proteins involved in these events are now known. However, a detailed picture of an entire trafficking organe...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2006.10.030
更新日期：2006-11-17 00:00:00
abstract：:A safe and controlled manipulation of endocytosis in vivo may have disruptive therapeutic potential. Here, we demonstrate that the anti-emetic/anti-psychotic prochlorperazine can be repurposed to reversibly inhibit the in vivo endocytosis of membrane proteins targeted by therapeutic monoclonal antibodies, as directly ...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2020.02.019
更新日期：2020-03-05 00:00:00
abstract：:The synthesis and secretion of plasminogen activator by cultured macrophages can be induced and stimulated by concanavalin A and by phorbol myristate acetate, and inhibited by such agents as glucocorticoids, mitotic inhibitors and compounds affecting cAMP metabolism. By the manipulation of stimulatory and inhibitory i...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(77)90086-1
更新日期：1977-07-01 00:00:00
